Zhou Bin, Ge Yugang, Shao Qing, Yang Liyi, Chen Xin, Jiang Guoqin
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu Province, China.
Department of Thyroid and Breast Surgery, The Affiliated Jiangyin Hospital of Southeast University Medical College, Wuxi, 214000, Jiangsu Province, China.
Cell Death Discov. 2021 Jun 26;7(1):156. doi: 10.1038/s41420-021-00551-8.
Accumulating evidence has suggested that long noncoding RNAs (lncRNAs) exert crucial modulation roles in the biological behaviors of multiple malignancies. Nonetheless, the specific function of lncRNA LINC00284 in papillary thyroid cancer (PTC) remains not fully understood. The objective of this research was to explore the influence of LINC00284 in PTC and elucidate its potential mechanism. The Cancer Genome Atlas (TCGA), gene expression omnibus (GEO) datasets were used to analyze LINC00284 expression differences in thyroid cancer and normal samples, followed by the verification of qRT-PCR in our own PTC and adjacent non-tumor tissues. The impacts of LINC00284 on PTC cell growth were detected in vitro via CCK-8, colony formation, EdU assays, and in vivo via a xenograft tumor model. Bioinformatics analyses and biological experiments were conducted to illuminate the molecular mechanism. We found that LINC00284 expression was remarkably increased in PTC tissues and its overexpression was closely correlated with larger tumor size. In addition, silencing LINC00284 could effectively attenuate PTC cell proliferation, induce apoptosis and G1 arrest in vitro, as well as suppress tumorigenesis in mouse xenografts. Mechanistic investigations showed that LINC00284 acted as a competing endogenous RNA (ceRNA) for miR-3127-5p, thus resulting in the disinhibition of its endogenous target E2F7. In short, our findings indicated that LINC00284-miR-3127-5p-E2F7 axis exerted oncogenic properties in PTC and may offer a new promising target for the diagnosis and therapy of PTC.
越来越多的证据表明,长链非编码RNA(lncRNA)在多种恶性肿瘤的生物学行为中发挥着关键的调节作用。然而,lncRNA LINC00284在甲状腺乳头状癌(PTC)中的具体功能仍未完全明确。本研究的目的是探讨LINC00284对PTC的影响并阐明其潜在机制。利用癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)数据集分析甲状腺癌和正常样本中LINC00284的表达差异,随后通过qRT-PCR在我们自己收集的PTC及癌旁非肿瘤组织中进行验证。通过CCK-8、集落形成、EdU实验在体外检测LINC00284对PTC细胞生长的影响,并通过异种移植肿瘤模型在体内进行检测。进行生物信息学分析和生物学实验以阐明分子机制。我们发现LINC00284在PTC组织中的表达显著增加,其过表达与更大的肿瘤大小密切相关。此外,沉默LINC00284可有效减弱PTC细胞增殖,在体外诱导细胞凋亡和G1期阻滞,并抑制小鼠异种移植瘤的肿瘤发生。机制研究表明,LINC00284作为miR-3127-5p的竞争性内源性RNA(ceRNA),从而导致其内源靶标E2F7的去抑制。简而言之,我们的研究结果表明LINC00284-miR-3127-5p-E2F7轴在PTC中发挥致癌作用,可能为PTC的诊断和治疗提供一个新的有前景的靶点。